The overall goal of this project is to develop and market a new topical treatment for acne that contains a 5-alkysulfonylsulfonylsalicylanilide as the active agent. The 5-alkylsulfonylsalicylanilides are a unique class of highly lipophilic compounds that possess both potent anti- inflammatory and antimicrobial activity against P. acnes while having virtually no potential for systemic toxicity. Topical pharmaceutical preparations containing 5-alkylsulfonylsalicylanilides are predicted to have utility in controlling acne by accumulating in sebum-filled papules and inhibiting inflammatory pathogenic bacteria as well as cell mediated inflammation. the specific goal of this proposal is to identify one "lead" and one "back-up" candidate compound from a small series of 5- alylsulfonylsalicylanilides. The compounds chosen will 1) be readily synthesized and formulated, 2) have maximum bioavailability and stability, 3) have a long term topical anti-microbial and anti- inflammatory efficacy (substantivity) and 4) exhibit no systemic toxicity when administered orally. In Phase II we intend to optimize formulations and determine long-term chemical, microbiological and physical stability. Additional safety and efficacy studies of the "lead" compound will be also conducted to support the filing of an IND application to the FDA for clinical studies beginning after the completion of Phase II. PROPOSED COMMERCIAL APPLICATION: Almost all people will have acne at some time in their life. Acne products are among the fastest growing over-the-counter medicinals sold at drug stores. In 1995 the total market for acne remedies was approximately $710 million. Many of the existing compounds which treat acne have side effects, some severe creating an outstanding marketing opportunity for drugs such as the 5-alkylsulfonylsalicylanidides, which are predicted to accomplish eradication without side effects.